Blood Brain Barrier Drug Delivery of Therapeutics for Chemical Warfare Agents

This program plans to develop a drug delivery system that provides maximum oxime drug exposure and improve cholinesterase reactivation in the brain and tissues of central nervous system (CNS) of a warfighter after exposure to organophosphate (OP) poisoning. The greatest need for improvement in cholinesterase reactivation is the ability to deliver charged cholinesterase reactivators to the CNS that do not readily cross the blood-brain barier (BBB). The current combination drug therapy requires infusion of high doses of drugs and is not well-suited for battlefield administration. Impel NeuroPharma has developed a novel non-invasive intranasal drug delivery technology that will bypass the BBB thereby allowing a maximum drug exposure and cholinesterase reactivation. Instead of depositing drugs to the lower nasal cavity (achieved with traditional nasal delivery devices), this technology deposits drugs into the upper 1/3 of the nasal cavity and provides direct access to the brain and CNS (via the olfactory cells), thereby improving the efficiency of CNS delivery. This proposed program will formulate oximes for delivery into the brain and CNS using this device and evaluating it in appropriate animal models. We envision that this product will be used in theater to counteract the effects of OP poisoning.